Localization of a small genomic region associated with elevated ACE.
(9/281)
Defining the relationship between multiple polymorphisms in a small genomic region and an underlying quantitative trait locus (QTL) represents a major challenge in human genetics. Pedigree analyses have shown that angiotensin I-converting enzyme (ACE) levels are influenced by a QTL located within or close to the ACE gene and most likely resides in the 3' region of this locus. We genotyped seven polymorphisms spanning 13 kb in the 3' end of ACE in 159 Afro-Caribbean subjects to evaluate the linkage disequilibrium between these sites and to narrow the genomic region associated with an elevated ACE level using a cladistic analysis. The linkage disequilibrium measurement D' and a haplotype tree revealed three distinct haplotype segments, presumably because of recombination. The value of the linkage disequilibrium parameter p(excess) was highest for site 22982, which is located in the middle segment. A series of nested, cladistic analyses confirmed that the other two regions are unlikely to be the ACE-linked QTL and that the variant resides in the middle region. Analyses of the same polymorphisms in 98 unrelated Europeans in the Monitoring Trends and Determinants in Cardiovascular Diseases (MONICA) study resulted in fewer haplotypes than were observed among the Afro-Caribbean subjects, suggesting that populations with greater genetic diversity may be especially informative for fine-scale mapping. (+info)
Selective screening for cervical neoplasia: an approach for resource-poor settings.
(10/281)
BACKGROUND: Cervical malignancies are the leading cause of cancer-related morbidity and mortality among women in developing countries. Although early detection programmes using cytological methods, followed by aggressive treatment of precursor lesions are accepted as the main disease control strategy, fiscal limitations make this strategy unfeasible in many countries. METHODS: To screen selectively, we developed two risk scores using data from a population-based case-control study in Jamaica with 202 cases and 363 controls. Independent risk factors for cervical neoplasia were determined using logistic regression. An unweighted risk score for each subject was developed by a simple count of risk factors present and a weighted risk score was calculated by summing regression coefficients for each risk factor. RESULTS: Four patient characteristics were independently predictive of cervical neoplasia, older age (OR = 3.4, 95% CI : 1.8-6.7), > or = 4 pregnancies (OR = 5.6, 95% CI : 1.2-18.7), poverty (OR = 2.1, 95% CI : 1.3-3.3) and cigarette smoking (OR = 1.9, 95% CI : 1.2-3.2). Using cut-off points of > or = 20 for the weighted scores and > 3 for unweighted scores, the sensitivity and specificity were 65% and 69% for the unweighted score and 75% and 61%, respectively, for the weighted score. Areas under the receiver operating characteristic (ROC) curves for the weighted versus the unweighted scores were similar, suggesting similar overall accuracy. CONCLUSION: Selective screening using risk assessment strategies is potentially useful, particularly in resource-poor settings. However, whether weighting factors is essential is dependent on prevalence of factors in a given setting. Although this approach needs validation in other populations, women at highest risk for cervical neoplasia can be identified using demographic factors available during a regular clinic visit. (+info)
In vitro antimicrobial susceptibility testing of bacterial enteropathogens causing traveler's diarrhea in four geographic regions.
(11/281)
The emergence of resistant enteropathogens has been reported worldwide. Few data are available on the contemporary in vitro activities of commonly used antimicrobial agents against enteropathogens causing traveler's diarrhea (TD). The susceptibility patterns of antimicrobial agents currently available or under evaluation against pathogens causing TD in four different areas of the world were evaluated. Pathogens were identified in stool samples from U.S., Canadian, or European adults (18 years of age or older) with TD during 1997, visiting India, Mexico, Jamaica, or Kenya. MICs of 11different antimicrobials were determined against 284 bacterial enteropathogens by the agar dilution method. Ciprofloxacin, levofloxacin, ceftriaxone, and azithromycin were highly active in vitro against the enteropathogens, while traditional antimicrobials such as ampicillin, trimethoprim, and trimethoprim/sulfamethoxazole showed high levels and high frequencies of resistance. Rifaximin, a promising and poorly absorbable drug, had an MIC at which 90% of the strains tested were inhibited of 32 microg/ml, 250 times lower than the concentration of this drug in the stools. Amdinocillin, nalidixic acid, and doxycycline showed moderate activity. Fluoroquinolones are still the drugs of choice for TD in most regions of the world, although our study has a limitation due to the lack of Escherichia coli samples from Kenya and possible bias in selection of the patients for evaluation. Azithromycin and rifaximin should be considered as promising new agents. The widespread in vitro resistance of the traditional antimicrobial agents reported since the 1980s and the new finding of resistance to fluoroquinolones in Southeast Asia are the main reasons for monitoring carefully the antimicrobial susceptibility patterns worldwide and for developing and evaluating new antimicrobial agents for the treatment of TD. (+info)
Characteristics of Helicobacter pylori infection in Jamaican adults with gastrointestinal symptoms.
(12/281)
Helicobacter pylori infection is common in Jamaica. Describing its epidemiology in a population-based study depends largely on serology, but serologic assays have not been validated in this population. To address this issue, we examined the presence of H. pylori infection in 30 sequential adult patients with gastroduodenal symptoms by three biopsy-based methods (rapid urease test, histology, and culture) as well as by one research and two commercial enzyme-linked immunosorbent assays (ELISAs). A patient was considered H. pylori positive if the organism was detected by at least one biopsy-based method. Eighteen (60%) of the 30 patients were H. pylori positive by these criteria, whereas 21 (70%) were seropositive for H. pylori immunoglobulin G by our research ELISA. The presence of H. pylori infection in patients with gastric cancer and those with chronic gastritis was missed by biopsy-based methods but was detected by serologic assays. This observation indicates that serologic assays may be better suited for the detection of this infection in a population in which H. pylori-associated pathology is prevalent. The performance of our research ELISA in detecting biopsy-based H. pylori-positive cases was excellent, with a sensitivity and specificity of 100% and 75%, respectively. Molecular genotyping of the isolates revealed that the predominant H. pylori genotypes in this cohort of Jamaicans were cagA(+) vacA slb-m1, and iceA2. The validated serologic assay enables us to interpret epidemiologic data from population-based studies in Jamaica by comparison to those from other populations. (+info)
Sick genes, sick individuals or sick populations with chronic disease? The emergence of diabetes and high blood pressure in African-origin populations.
(13/281)
AIM AND METHODS: To discuss evidence for and against genetic 'causes' of type 2 diabetes, illustrated by standardized study of glucose intolerance and high blood pressure in four representative African origin populations. Comparison of two genetically closer sites: rural (site 1) and urban Cameroon (2); then Jamaica (3) and Caribbean migrants to Britain (80% from Jamaica-4). BACKGROUND: Alternatives to the reductionist search for genetic 'causes' of chronic disease include Rose's concept that populations give rise to 'sick' individuals. Twin studies offer little support to genetic hypotheses because monozygotic twins share more than genes in utero and suffer from ascertainment bias. Non-genetic intergenerational mechanisms include amniotic fluid growth factors and maternal exposures. Type 2 diabetes and hypertension incidence accelerate in low-risk European populations from body mass > or =23 kg/m2, well within 'desirable' limits. Transition from subsistence agriculture in West Africa occurred this century and from western hemisphere slavery only six generations ago, with slow escape from intergenerational poverty since. RESULTS: 'Caseness' increased clearly within and between genetically similar populations: age-adjusted diabetes rates were 0.8, 2.4, 8.5 and 16.4% for sites 1-4, respectively; for 'hypertension', rates were 7, 16, 21 and 34%, with small shifts in risk factors. Body mass index rose similarly. CONCLUSION: Energy imbalance and intergenerational socioeconomic influences are much more likely causes of diabetes (and most chronic disease) than ethnic/genetic variation, which does occur, poorly related to phenotype. The newer method of 'proteomics' holds promise for identifying environmental triggers influencing gene products. Even in lower prevalence 'westernized' societies, genetic screening per se for diabetes/chronic disease is likely to be imprecise and inefficient hence unreliable and expensive. (+info)
Recovery of Diadema antillarum reduces macroalgal cover and increases abundance of juvenile corals on a Caribbean reef.
(14/281)
The transition of many Caribbean reefs from coral to macroalgal dominance has been a prominent issue in coral reef ecology for more than 20 years. Alternative stable state theory predicts that these changes are reversible but, to date, there is little indication of this having occurred. Here we present evidence of the initiation of such a reversal in Jamaica, where shallow reefs at five sites along 8 km of coastline now are characterized by a sea urchin-grazed zone with a mean width of 60 m. In comparison to the seaward algal zone, macroalgae are rare in the urchin zone, where the density of Diadema antillarum is 10 times higher and the density of juvenile corals is up to 11 times higher. These densities are close to those recorded in the late 1970s and early 1980s and are in striking contrast to the decade-long recruitment failure for both Diadema and scleractinians. If these trends continue and expand spatially, reefs throughout the Caribbean may again become dominated by corals and algal turf. (+info)
Trans-ethnic fine mapping of a quantitative trait locus for circulating angiotensin I-converting enzyme (ACE).
(15/281)
Circulating angiotensin I-converting enzyme (ACE) levels are influenced by a major quantitative trait locus (QTL) that maps to the ACE gene. Phylogenetic and measured haplotype analyses have suggested that the ACE-linked QTL lies downstream of a putative ancestral breakpoint located near to position 6435. However, strong linkage disequilibrium between markers in the 3' portion of the gene has prevented further resolution of the QTL in Caucasian subjects. We have examined 10 ACE gene polymorphisms in Afro-Caribbean families recruited in JAMAICA: Variance components analyses showed strong evidence of linkage and association to circulating ACE levels. When the linkage results were contrasted with those from a set of British Caucasian families, there was no evidence for heterogeneity between the samples. However, patterns of allelic association between the markers and circulating ACE levels differed significantly in the two data sets. In the British families, three markers [G2215A, Alu insertion/deletion and G2350A] were in complete disequilibrium with the ACE-linked QTL. In the Jamaican families, only marker G2350A showed strong but incomplete disequilibrium with the ACE-linked QTL. These results suggest that additional unobserved polymorphisms have an effect on circulating ACE levels in Jamaican families. Furthermore, our results show that a variance components approach combined with structured, quantitative comparisons between families from different ethnic groups may be a useful strategy for helping to determine which, if any, variants in a small genomic region directly influence a quantitative trait. (+info)
Enteroaggregative Escherichia coli as a major etiologic agent in traveler's diarrhea in 3 regions of the world.
(16/281)
Enteroaggregative Escherichia coli (EAEC) has been reported to cause traveler's diarrhea and persistent diarrhea in children in developing countries and in immunocompromised patients. To clarify the prevalence of EAEC in traveler's diarrhea, we studied 636 US, Canadian, or European travelers with diarrhea: 218 in Guadalajara, Mexico (June--August 1997 and 1998), 125 in Ocho Rios, Jamaica (September 1997--May 1998), and 293 in Goa, India (January 1997--April 1997 and October 1997--February 1998). Stool samples were tested for conventional enteropathogens. EAEC strains were identified by use of the HEp-2 assay. EAEC was isolated in 26% of cases of traveler's diarrhea (ranging from 19% in Goa to 33% in Guadalajara) and was second only to enterotoxigenic E. coli as the most common enteropathogen in all areas. Identification of EAEC reduced the number of cases for which the pathogen was unknown from 327 (51%) to 237 (37%) and explained 28% of cases with unknown etiology. EAEC was a major cause of traveler's diarrhea in 3 geographically distinct study areas. (+info)